Several synthetic hydrazines, including some used in rocket fuels, in agriculture, and in medicine, have proved to be tumorigenic in animals, and therefore are possible cancer causative agents in man. Only limited information is now available on the metabolism of the most prominent of these compounds in our environment, such as hydrazine, methylhydrazine, hydroxyethylhydrazine, and maleic hydrazide. Two of these compounds, hydrazine and methylhydrazine, are also either metabolites of therapeutically useful drugs or are undergoing evaluation as potentially useful drugs. The possible role of metabolism in promoting the tumorigenic response of these hydrazines will be explored by identifying those metabolites that are excreted by animals susceptible to their carcinogenicity, and by monitoring the alkylation of nucleic acids and proteins in the target organ for those metabolites that are too reactive to isolate. Specific deuterium labeling will be used to examine possible isotope effects on the carcinogenicity and metabolism of methylhydrazine, a rocket fuel propellant, and 1,2-dimethylhydrazine, a carcinogen that promotes the development of colon tumors by its metabolic activation to a potent alkylating agent. Because of the short time periods involved in studying the phenomenon of acute toxicity (i.e., cellular necrosis), the effects of altering metabolism on acute toxicity are more amenable to investigation than such effects on carcinogenicity. Therefore, attempts will be made to develop acute models of toxicity for the selected carcinogenic hydrazines. Those parameters that modulate metabolism will then be studied with reference to the toxic response. Attempts also will be made to determine if the Ames test will detect mutagenicity caused by hydrazines that are known carcinogens. If a procedure can be developed, then those chemical and biochemical factors that affect mutagenicity will be examined in order to help evaluate their possible role in initiating carcinogenic events.